title: Transforming growth factor β1 is not a reliable biomarker for valvular fibrosis but could be a potential serum marker for invasiveness of prolactinomas (pilot study).
abstract: BACKGROUND
  Transforming growth factor β1 (TGFβ1) signaling pathway is crucial for both human fibrogenesis and tumorigenesis.
  
  
  OBJECTIVE
  This study aimed to investigate the usefulness of TGFβ1 and matrix metalloproteinase 2 (MMP2) as potential circulating markers for fibrotic valvular heart disease (FVHD) and invasiveness as well as of Fetuin A as a marker for calcification in patients with prolactinomas.
  
  
  METHODS
  The study population consisted of 147 subjects divided into four groups: 30 dopamine agonist (DA)-treated prolactinoma patients with proven FVHD and three control groups with normal echocardiograms: 43 DA-treated patients, 26 naïve patients, and 48 healthy subjects.
  
  
  RESULTS
  We observed significantly higher serum TGFβ1 levels in all three patient groups than in the healthy subjects (21.4 ± 8.86 vs 19.1 ± 9.03 vs 20.7±11.5 vs 15.8 ± 7.2 ng/ml; P=0.032). Moreover, TGFβ1 levels were significantly higher in patients with macroprolactinomas and invasive prolactinomas than in those with microprolactinomas and noninvasive tumors respectively. In addition, a strong positive linear relationship between TGFβ1 levels and invasiveness score (ρ=0.924; P<0.001) and a moderate correlation between TGFβ1 levels and tumor volume (r=0.546; P<0.002) were observed in patients with invasive prolactinomas. By contrast, prolactin (PRL) levels exhibited a better correlation with tumor volume (r=0.721; P<0.001) than with invasiveness score (ρ=0.436; P<0.020). No significant difference was observed in Fetuin A levels between patients with FVHD and healthy controls. Results concerning MMP2 were unclear.
  
  
  CONCLUSIONS
  TGFβ1, MMP2, and Fetuin A are not reliable biomarkers for valvular fibrosis and calcification in DA-treated patients with prolactinomas, but TGFβ1 may represent a useful serum marker for tumor invasiveness. The simultaneous determination of TGFβ1 and PRL levels could improve the noninvasive assessment of prolactinoma behavior.
authors.affiliation: Clinical Centre of Endocrinology, USHATE Acad Ivan Pentchev, Medical University, 2 Zdrave Street, Sofia, Bulgaria. atanaskae@yahoo.com
authors.forename: Atanaska
authors.initials: A
authors.lastname: Elenkova
authors.forename: Iliana
authors.initials: I
authors.lastname: Atanassova
authors.forename: Georgi
authors.initials: G
authors.lastname: Kirilov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vasilev
authors.forename: Krassimir
authors.initials: K
authors.lastname: Kalinov
authors.forename: Sabina
authors.initials: S
authors.lastname: Zacharieva
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D016022:Case-Control Studies; D015331:Cohort Studies; D018491:Dopamine Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis; D006349:Heart Valve Diseases / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D006351:Heart Valves / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010865:Pilot Projects; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D010911:Pituitary Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D015175:Prolactinoma / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000097:blood*; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018491:Dopamine Agonists; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1